VISIÓN Y FUTURO

CÁNCER DE PULMÓN

ROSARIO GARCIA CAMPELOMedical Oncology Unit

University Hospital A Coruña. INIBIC @Charocampelo

• Advisory Board/Consultancy/Speaker honoraria: MSD, Bristol-Myers,Roche, Boehringer Ingelheim, Pfizer, Novartis, Astra-Zeneca, Lilly, Takeda

• Employment: None

DISCLOUSURES

EL OFICIO DEL MÉDICO

CURAR

CUIDAR

INVESTIGAR

EL RETO DE LA

SOSTENIBILIDAD/

COSTE

EL RETO DE LAS

CIFRAS

EL RETO DE LA

EQUIDAD

EL RETO DEL PACIENTE

COMO EJE

FUNDAMENTAL

EL RETO DE LA

Prevención y

dx precoz

EL RETO DE LA

COMPLEJIDAD DEL

CÁNCER

Loss of productivity in Spain due to lung cancer:13.100.000.000 € (2008-18)BMC Cancer (2019) 19:992 https://doi.org/10.1186/s12885-019-6243-7

Impact lung cancer in Spain

Axiome for Pharmaeconomics in

Oncology:

All improvements in outcomes means

increase in directs healthcare costs

New cancer drugs are priced beyond monthly household income in USA / Financial Toxicity

Prasad et al Nat Rev Clin Oncol 2017

How will we achieve sustainability?

EL RETO DE LA

SOSTENIBILIDAD/

COSTE

EL RETO DE LAS

CIFRAS

EL RETO DE LA

EQUIDAD

EL RETO DEL PACIENTE

COMO EJE

FUNDAMENTAL

EL RETO DE LA

Prevención y

dx precoz

EL RETO DE LA

COMPLEJIDAD DEL

CÁNCER

Access and expenditures need to be improved

https://www.europeancancerleagues.org/wp-content/uploads/ECL-Lets Talk-Access-White-Paper.pdf (Accessed 26th June 2019) * Vrodoljak – The Oncologist 2019 (Slide courtesy of Dr Novello, modified)

Cancer drugs are available less

often in Central and Eastern Europe

Health expenditure is lower and mortality is

higher in Central and Eastern Europe (CEE)

Availability of cancer drugs in Western Europe vs. CEE: 91% vs. 70%

Delays in access to effective new cancer drugs

http://www.europe-economics.com/publications/external_reference_pricing_-_final_report.pdf. Accessed 022018. (Courtesy Dr Novello)https://www.europeancancerleagues.org/wp-content/uploads/ECL-Lets Talk-Access-White-Paper.pdf (Accessed 26th June 2019)

Average launch delays for inpatient

oncology drugs: 2001–2013

Retraso rapidez e incorporación nuevos fármacos

Desde la fijación de precio/reembolso

Desde la autorización por parte de la Comisión Europea

Barreras en la prescripción

Un país… 17 realidades distintasINFORME SEOM 2019

EL RETO DE LA

SOSTENIBILIDAD/

COSTE

EL RETO DE LAS

CIFRAS

EL RETO DE LA

EQUIDAD

EL RETO DEL PACIENTE

COMO EJE

FUNDAMENTAL

EL RETO DE LA

Prevención y

dx precoz

EL RETO DE LA

COMPLEJIDAD DEL

CÁNCER

¿CÓMO ABORDAR ESTA “EPIDEMIA” DEL CÁNCER DE PULMÓN?

PREVENCIÓN

FACTORES DE RIESGO

2%Polución ambiental 8%

Asbesto

8-10%Exposición

Radon

9-15%Exposición

ocupacional

85%TABACO

Lung Cancer Risk

lung

cancer

?

Rapid developmentof molecular

targeting agents

The masiveavailability of IO

Clinical application of plasma/ tissue based

genomic testing

Jordan EJ, et al. Cancer Discov 2017

Molecular subtyping of pulmonary adenocarcinoma in 2018

• 860 patients• Prospective analysis of >300 cancer-associated genes

87% of potentially actionable alterations

Mo, months; OS, overall survival; PFS, progression-free survival.1. Rosell R, et al. Lancet Oncol 2012;13:239–46; 2. Tarceva (erlotinib) Summary of Product Characteristics. Last updated April 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/tarceva-epar-product-information_en.pdf; 3. Zhou C, et al. Ann Oncol 2015;26(9):1877–83; 4. Wu YL, et al. Ann Oncol 2015;26(9):1883–9; 5. Mitsudomi T, et al. Lancet Oncol 2010;11(2):121–8; 6. Iressa (gefitinib) Summary of Product Characteristics. Last updated May 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/iressa-epar-product-information_en.pdf ; 7. Inoue A, et al. Ann Oncol 2013;24(1):54–9; 8. Han JY, et al. J Clin Oncol 2012;30(10):1122–8; 9. Wu YL, et al. Asia Pac J Clin Oncol 2012;8(3):232–43; 10. Sequist LV, et al. J Clin Oncol 2013;31:3327–34; 11. Giotrif (afatinib) Summary of Product Characteristics. Last updated July 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/giotrif-epar-product-information_en.pdf; 12. Wu YL, et al. Lancet Oncol 2014;15(2):213–22; 13. Paz-Ares L, et al. Ann Oncol 2017;28:270–7; 14. Wu Y-L, et al. Lancet Oncol 2017;18(11):1454–66; 15. Vizimpro (dacomitinib) Summary of Product Characteristics. Last updated June 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/vizimpro-epar-product-information_en.pdf; 16. Soria JC et al. N Engl J Med 2018;378:113–25; 17. Tagrisso (osimertinib) Summary of Product Characteristics. Last updated September 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/tagrisso-epar-product-information_en.pdf (All SmPCs accessed September 2019).

PFS comparison of first- and second-generation TKIs vs third-generation TKIs

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Afatinib

Erlotinib

Gefitinib

Dacomitinib

Osimertinib

2nd > 1st

PFS 11-15 moOS ~ 34 mo

1st & 2nd > QTPFS ~ 11 mo

OS ~ 25–30 mo

3rd > 1st

PFS 18.9 moOS 38.6 mo

Afatinib Erlotinib Gefitinib

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A+E/G Dacomitinib Osimertinib Ramu+Erl

How to Integrate the Results of RELAY in the Current

Landscape of EGFR Mutant Treatment?

Mo, months; OS, overall survival; PFS, progression-free survival.1. Rosell R, et al. Lancet Oncol 2012;13:239–46; 2. Tarceva (erlotinib) Summary of Product Characteristics. Last updated April 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/tarceva-epar-product-information_en.pdf; 3. Zhou C, et al. Ann Oncol 2015;26(9):1877–83; 4. Wu YL, et al. Ann Oncol 2015;26(9):1883–9; 5. Mitsudomi T, et al. Lancet Oncol 2010;11(2):121–8; 6. Iressa (gefitinib) Summary of Product Characteristics. Last updated May 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/iressa-epar-product-information_en.pdf ; 7. Inoue A, et al. Ann Oncol 2013;24(1):54–9; 8. Han JY, et al. J Clin Oncol 2012;30(10):1122–8; 9. Wu YL, et al. Asia Pac J Clin Oncol 2012;8(3):232–43; 10. Sequist LV, et al. J Clin Oncol 2013;31:3327–34; 11. Giotrif (afatinib) Summary of Product Characteristics. Last updated July 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/giotrif-epar-product-information_en.pdf; 12. Wu YL, et al. Lancet Oncol 2014;15(2):213–22; 13. Paz-Ares L, et al. Ann Oncol 2017;28:270–7; 14. Wu Y-L, et al. Lancet Oncol 2017;18(11):1454–66; 15. Vizimpro (dacomitinib) Summary of Product Characteristics. Last updated June 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/vizimpro-epar-product-information_en.pdf; 16. Soria JC et al. N Engl J Med 2018;378:113–25; 17. Tagrisso (osimertinib) Summary of Product Characteristics. Last updated September 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/tagrisso-epar-product-information_en.pdf (All SmPCs accessed September 2019).

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Afatinib

Erlotinib

Gefitinib

Dacomitinib

Osimertinib

2nd > 1st

PFS 11-15 moOS ~ 34 mo

1st & 2nd > QTPFS ~ 11 mo

OS ~ 25–30 mo

3rd > 1st

PFS 18.9 moOS 38.6 mo

31st+QT

PFS 20.9 moOS 52.2mo

Osimertinib

How to Integrate the Results of EGFR TKI+QT in the Current

Landscape of EGFR Mutant Treatment?

Crizotinib1

Brigatinib*3

Lorlatinib‡6

1st generation

2nd

generation

3rd generation

Alectinib2

Ceritinib4

Ensartinib†5

Next generation ALK TKIs

Treatment options for ALK-positive NSCLC

*Ensartinib is not approved by the EMA for use in NSCLC.†Brigatinib is centrally authorised in the EU after crizotinib failure but not yet marketed in Spain pending pricing and reimbursement approval.‡Lorlatinib is centrally authorised in the EU but not yet marketed in Spain pending pricing and reimbursement approval.1. Xalkori© (crizotinib) SmPC. Updated April 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/xalkori-epar-product-information_en.pdf; 2. Alecensa© (alectinib) SmPC. Updated July 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/alecensa-epar-product-information_en.pdf; 3. Alunbrig© (brigatinib) SmPC. Updated February 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/alunbrig-epar-product-information_en.pdf; 4. Zykadia© (ceritinib) SmPC. Updated August 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/zykadia-epar-product-information_en.pdf; 5. Clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT02767804; 6. Lorviqua (lorlatinib) Summary of Product Characteristics. 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/lorviqua-epar-product-information_en.pdf (All accessed September 2019).

• Is there a difference in survival benefit between these two regimens?

• Is there a role for 3rd-generation in the first-line?

PD, progressive disease.

Evolving treatment strategy for metastatic ALK+ NSCLC

Crizotinib Ceritinib2nd-generation ALKi

PDALK resistance mutation,

including ALK G1202R

Crizotinib 2nd-generation ALK TKI 3rd-generation ALK TKI

2nd-generation ALK TKI 3rd-generation ALK TKI

EGFR, ALK, ROS, BRAF15%-20

PD-L1 1-49% 40%

PD-L1 <50%30%

Believers or non believers…

ORR: 20-30%mPFS: 5-6 monthsmOS: 8-10 months

2 year survival rate: 11%5 year survival rate: 0%

ALK +NSCLCUNSELECTED POPULATION

Median OS 88.44m

*FDA approved; †Not approved by the EMA for use; ‡Not approved for use in NSCLC.1. Xalkori© (crizotinib) SmPC. Updated April 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/xalkori-epar-product-information_en.pdf; 2. ROZLYTREK (entrectinib). Prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212725s000lbl.pdf; 3. Lorviqua (lorlatinib) Summary of Product Characteristics. Last updated June 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/lorviqua-epar-product-information_en.pdf; 4. Cabometyx (Cabozantinib) SmPC. Updated January 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf; 5. Alunbrig© (brigatinib) SmPC. Updated February 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/alunbrig-epar-product-information_en.pdf; 6. Zykadia© (ceritinib) SmPC. Updated August 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/zykadia-epar-product-information_en.pdf; 7. Rolfo C, et al. Expert Opin Investig Drugs 2015;24:1493–500; 7. TP Therapeutics Press Release: businesswire.com/news/home/20170627005421/en/TP-Therapeutics-Announces-FDA-Orphan-Drug-Designation; 8. Clinical Trial NCT02675491: clinicaltrials.gov/ct2/show/NCT02675491. (All accessed September 2019)

ROS1 inhibitor summary

Crizotinib1Approved ROS1 inhibitor

Potential ROS1 inhibitors under investigation

Brigatinib †5Lorlatinib†3

Repotrectinib†

7

Ceritinib†6

Entrectinib*2

Cabozantinib**4

DS-6051b†8

Slide 5

Slide 13

ORR 48%-54%mDOT 10-15.1w

AMG 510: a novel KRAS G12C inhibitorLET´S TALK ABOUT AN OLD FRIEND

New Targets Finally hope with KRAS (G12C)

Govindan et al. ESMO 2019

MET aberrations NSCLC

MET mutant / amplified NSCLC, poor Px.

MET as a primary driver

MET as a secondary / co-driver

26%

~70 years. 68% female. 53% smokers

Type I

(binds to active kinase form)

Type II

(binds to inactive kinase form)

crizotinib capmatinib tepotinib savolitinib cabozantinib merestinib glesatinib

22 0.6 3.0 2.1 7.8 8.1 21

IC50 of each MET-TKI (nM)

MET exon14 mutation

Drilon – WCLC 2018 * Moro-Sibilot – Ann Oncol 2019 * Wolf - ASCO 2019 * Paik – ASCO 2019 * Lu – AACR 2019

CRIZOTINIB CAPMATINIBGEOMETRY

TEPOTINIB*VISION

SAVOLITINIB

PROFILE ACSE 1ST LINE ≥ 2ND LINE 1ST LINE ≥ 2ND LINE 55% ≥ 2 Lines

N 69 25 28 69 33 31 31

RR (%) 32 40 68 41 44 50 52

DoR (mo.) 9.1 NR 11.1 9.7 12.4 NR

PFS (mo.) 7.3 3.6 9.7 5.4 10.8 NR

OS (mo.) 20.5 8.1 NR NR NR NR

*data in tissue by BIR. NR: not reported

FDA29th May 2018

FDA breakthrough therapy designation6th and 11st Sept 2019, respectively

Courtesy J. Remón

ONE DRUG FITS ALL

Genomic profiling and agnostic approvalsMolecular alterations shared in several cancers

Gainor et al ASCO 2019 Hyman et al. ASCO 2017

LIBRETTO 001 TRIALLOXO 292

Drilon A, et al. WCLC 2019

Prior Platinum doublet (n=105)ORR 68%CNS ORR 91%mDoR 20.3mmPFS 18.4m

Treatment Naive (n=34)ORR 85%DoR NRPFS NR

RXDX-105 in RET NSCLCVEGFR-sparing, multikinase inhibitor with activity against RET

Drilon et al Cancer Disc 2019

RXDX-1505. N=22 RET TKI naive

RR KIF5B: 0%RR Non-KIF5B: 67%

NTRKThe main actors…

Lassen, ESMO 2018

Drilon A, et al. ASCO 2019

Larotrectinib

Integrated dataset

ORR 81%

ORR 60% ORR 75%mDOT 9.2 m

Farago A, et al. WCLC 2019

Activity of Larotrectinib in TRK Fusion Lung Cancer

Entrectinib

Integrated analysis

Rolfo C, et al. ESMO 2019

ORR 59.3%mDoR 12.9mmPFS 11.8mmOS 23.9m

Entrectinib

Integrated analysis

Paz-Ares ELCC 2019

Doebele et al. AACR 2019

ORR 70%mPFS 14.9micORR 67%

Paz-Ares L, et al. WCLC 2019

LOXO 195: a 2nd generation TRK inhibitor

Hyman D, et al. AACR 2019

NSCLC: RR 34%

• Initially identified in invasive mucinous adenocarcinoma (IMA) lung1

• Rare gene fusions:– Incidence: 0.2% across all solid tumors2

– Invasive mucinous adenocarcinomas (IMAs) of lung: 27-31%3

– KRAS WT pancreatic cancer4, ovarian, breast cancer, multiple others2

• Mechanism based on oncogenic signaling of HER2/HER3 hetero-dimerization

• Case reports of responses to afatinib although unclear ORR or PFS5

– Proof of principle of HER2-inhibition mechanism

New Targets: NRG1 gene fusions

1Fernandez-Cuesta et al., Cancer Discov 2014; 2Jonna et al, Clin Can Res 2019; 3Shin et al, Mol Cancer Ther. 2018; 4Jones et al., Clin Can Res 2019; 5Jones et al., Annals of Oncology 2017; 6Dimou and Camidge, Clin Can Res 2019

MOVING BEYOND THE PRIMARY ONCOGENE DRIVER

Unique mutation subsets, concomitant mutations…

Classically thought to be “simple” tumors…now we have an improved understandingNot all EGFR mutations are the same: coexistance of concomitant alterations

Childress – Mol Cancer Res 2018

Lin et al. JCO 2018

ALK variant partner related to crizotinib efficacyand specific risk of ALK-mutations onset (G1202R)

ALK fusion partner and ALK TKI activity

Variant 3 the longer PFS on Lorlatinib

ALK fusion partner and Ensartinib activity

Horn L et al. ELCC 2019Camidge R, et al J Thorac Oncol 2019

Diving into the next layer of genomic complexicity: The mutation type matters!

Many patients initiate treatment based on IHC ALK alone

The amazing speed of positive results in early, locally advanced and

advanced NSCLC

Early Stage Locally advanced Stage IVPD-L1>50%

Stage IVAll comers

Antonia S, NEJM 2018, Brahmer J, et al. WCLC 2017, Gandhi L et al. NEJM 2018; Reck M, et al. WCLC 2019

An impressive number of positive Phase III trials in

advanced lung cancer

Plai

KN 407Impower 131

Impower 132Impower 130

Impower 150

KN 189

IO+IO Poseidon

Mystic

CM 227

IO

Monotherapy

Impower 110

KN 024

CM 026KN 042

Las terapias dirigidas mejoran los resultados clínicos para tipos específicos de mutación

The potential options

I0+/-IO+CT

ALTA 1L

THE ELEMENTS FOR

DECISSION• Efficacy Data

• Safety Data

The data

• Age

• PS

• Smoking

• Comorbilities

• Contraindications for IO

• Patient preference

The patient

• Liver metastasis

• Brain Metastasis

• Disease Burden

Disease

• Histology

• EGFR, ALK, ROS, BRAF, MET mutations

• PD-L1 expression

• TMB

• Other biomarkers (LKB1, KEAP, ARIAD 1, KRAS…)

The tumor

Predictive Biomarkers for Checkpoint Immunotherapy (CPI)

Gandara: Lung Cancer Summit. ESMO19

• What is the context? (Biomarker for which type of CPI regimen)• NSCLC (Squamous or Non-Squamous) vs SCLC• CTLA-4 vs PD-1/PD-L1 vs PD-1/PD-L1 + CTLA-4• PD-1/PD-L1 + Platinum Chemotherapy

• Which Biomarker(s)? • PD-L1 IHC• TMB• PD-L1 IHC + TMB• PD-L1 + TMB + Other• Multitude of Others

Chemotherapy likely “agnostic” to immuno-biomarker .

“Dilutes out predictive value

Note: cannot be equated to a discrete variable like driver mutations (Present or Absent)PD-L1/TMB are dynamic & continuous variables across a context-specific range

As a Binary Variable

Samstein et al: NatGen 2018

TMB highest 10-20% across Tumor Types

• Which Analytic Algorithm for Analysis? • Across a Continuous Range • As a Binary Variable

Gandara et al: NatMed 2018

Blood TMB:PFS in OAK trial

Continuous Range

FIRST-LINE METASTATIC NSCLC

Is there an optimal duration for combination chemo-immunotherapy?

Do these data translate to patient subgroups excluded from phase III clinical trials

What to offer after first-line combination therapy fails?

How to improve predictive biomarkers to better select patients for each approach?

So many unsolved issues…

AND ALL YOU MAY HAVE AND WANT TO SHARE..

Try to stablish the best sequence with almost 4000 agents in development…and more than 1000 combination trials

The next frontier: Understanding and Overcoming resistance to TargetedTherapy and Immunotherapy

• Govindan, Science 2014

Clonal heterogeneity

over time

Spatial heterogeneity at given

timepoint

Major limitation of molecularly guided sequential therapy:

tumor heterogeneity

Govindan, R, et al. Attack of the clones. Science, 346(6206),169-170. doi: 10.1126/science.1259926

Freq. Δ

Best response

3rd gen. EGFR TKI

Baseline

T790M 100%

G724S NA NA NA NAi NA 2%

C797S NA NA NA NAi NAi 0%

TP53 NA NA NA NAi NA i 47%

CTNNB1 NA NA NA NAi NAi 6%

PTEN NA NA NA NAi NAi 4%

PIK3CA NA NA NA NAi NAi 4%

KRAS NA NA NA NAi NAi 0%

BRAF NA NA NA NAi NAi 0%

MET NA NANANA NA NA NANA iNA 9%

HER2 NA NANANANA NA NANANA NA NANA NA i 7%

T790M 55% -45%

G724S i 11% +7%

C797S 12% +12%

TP53 iNAi i 54% +4%

CTNNB1 iNAi i 11%

PTEN iNAi i 7% +4%

PIK3CA iNAi i 4%

KRAS iNAi i 7% +7%

BRAF iNAi i 4% +4%

MET NANAi 26% +26%

HER2 NANAi 7% +7%

PR Osimertinib Del19 WT Not done

SD Rociletinib L858R Missense/nonsense Changes found

PD EGF816 Other Amplified No changes found

Cohort B

(n=56)

EGFR

Cohort C

(n=29)

PD (12.5%)

SNV

SCNA

PR (60.7%; 95% CI 46.8-73.5) SD (26.8%)

EGFR

Changes found 86%

SNV

SCNA

Genomic profiling identifies outcome-relevant mechanisms of innate and acquired resistance 3rd gen EGFR TKI

Michels et al, JCO Prec Onc 2019

Acquired resistance to

1st gen. EGFR-TKI

Acquired resistance to

3rd gen. EGFR-TKI

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sin

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en

etic

he

tero

ge

ne

ity

Cellular ALK Phosphorylation Mean IC50 (nM)

Mutation status Crizotinib Ceritinib Alectinib Brigatinib Lorlatinib

EML4-ALK 38.6 4.9 11.4 10.7 2.3

C1156Y 61.9 5.3 11.6 4.5 4.6

I1171N 130.1 8.2 397.7 26.1 49.0

I1171S 94.1 3.8 177.0 17.8 30.4

I1171T 51.4 1.7 33.6 6.1 11.5

F1174C 115.0 38.0a 27.0 18.0 8.0

L1196M 339.0 9.3 117.6 26.5 34.0

L1198F 0.4 196.2 42.3 13.9 14.8

G1202R 381.6 124.4 706.6 129.5 49.9

G1202del 58.4 50.1 58.8 95.8 5.2

D1203N 116.3 35.3 27.9 34.6 11.1

E1210K 42.8 5.8 31.6 24.0 1.7

G1269A 117.0 0.4 25.0 ND 10.0

IC50 ≤50 nM IC50 >50–<200 nM IC50 ≥200 nM

Adapted from Gainor JF, et al. Cancer Discov. 2016;6:1118–33.

• Secondary mutations in the

ALK kinase domain can

induce resistance to first-

and second-generation ALK

TKIs1

• Lorlatinib has broad-

spectrum potency against

most known ALK resistance

mutations, including ALK

G1202R1,2

Lorlatinib Covers the Broadest Range of ALK Resistance Mutations

IC50, half-maximal inhibitory concentration; ND, not done

1. Gainor JF, et al. Cancer Discov. 2016;6:1118–1133.

2. Johnson TW, et al. J Med Chem. 2014;57:4720–4744.

On/ off target resistance to new ALK inhibitors

Lee et al. WCLC 2019Recondo et al. Clin Cancer Res 2019

Mechanisms of Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14 Mutant Non-Small Cell Lung Cancer Summary of resistance mechanisms and clinical outcomes

Recondo et al. WCLC 2019

Off target resistance to NTRKi

Cocco et al. Nature Med 2019

The main issue with IO…

Gettinger et al. J Clin Oncol 2018

CLINICAL SCENARIOS FOR RESISTANCES

Padmanee Sharma, Cell 2017

Primary Adaptive

Acquired

Sharma P, Cell 2017

IO: Tumor & Host Dependent

Hudson trial NCT03334617; sponsor: AstraZenecaPIONeeR trial NCT03833440;; Barlesi F, et al. WCLC 2019

Morpheus trial NCT03337698; sponsor: Roche Syn et al. Lancet Oncol17

HU

DSO

NM

OR

PH

EUS

PIO

Nee

RTE

DO

PI

A FRAMEWORK FOR UNDERSTANDING DRUG RESISTANCE

Vasan N, et al. Nature 2019

PROPOSED SOLUTIONS TO THE PROBLEM OF DRUG RESISTANCE IN CANCER

Vasan N, et al. Nature 2019

One of the main challenges

TESTING

According to guidelines…The “must do it”…and “if you can do it” effect

The must do it…

If you can do it…

Garrido P, et al. Clin Transl Oncol 2019

Rodriguez-Abreu D et al. SEOM 2019

SPANISH THORACIC TUMORS REGISTRYBIOMARKER ANALYSIS

El porcentaje de determinaciones moleculares ha

variado a lo largo del tiempo, desde 57.9% antes de 2012 hasta 73.7% en 2017

•Genotyping:•QualityReproducibility

Unrestricted access

Adequate turn-around time

If “you can do it effect”

Morganti S, et al. Crit Rev Oncol 2019

French National INCA platformOperated by INCa/Ministry of Health since 2006

Objective:• Perform molecular

testing for all patients• Perform high quality

tests

28 regional centres• Partnerships between several

laboratories located in Universityhospitals and cancer centres

• Cooperation between pathologistsand biologists

SO MANY VARIABLES…What is your local context?

Where do you practice? What are the constraints?

Stoekle HC et al. Sci Eng Ethics 2018

MTBs are the logical evolution of the traditional tumor boards in the era of genomic medicine

• Expert teams

• Sample availability: biopsy, rebiopsy…

• Technology

• Bioinformatics

• Adequate time-frame

• Quality assurance programs

• Link to a innovative clinicaltrials program

EL RETO DE LA

SOSTENIBILIDAD/

COSTE

EL RETO DE LAS

CIFRAS

EL RETO DE LA

EQUIDAD

EL RETO DEL PACIENTE

COMO EJE

FUNDAMENTAL

EL RETO DE LA

Prevención y

dx precoz

EL RETO DE LA

COMPLEJIDAD DEL

CÁNCER

CLARIFY EXPECTATIONS…

What do patients -and the world- consider

MEANINGFUL CLINICAL BENEFIT?

LET´S CHECK OUR ENTHUSIASM…WE ARE NOT CURING ANYBODY

• Clinical characteristics

• Better educational background

• Good information access

• New culture patient= costumer

• Active implication in self care strategies

• Health= individual right

• More participation in health decision

A GOOD DOCTOR TREATS A DISEASE…A GREAT DOCTOR TREATS

THE PATIENT WITH A DISEASE

DroughtMysterious, fascinatingHope for the future